文章：

为前列腺癌中联合雄激素靶向疗法的自噬抑制治疗策略提供依据

Making the Case for Autophagy Inhibition as a Therapeutic Strategy in Combination with Androgen-Targeted Therapies in Prostate Cancer

原文发布日期：18 October 2023

DOI: 10.3390/cancers15205029

类型: Article

开放获取: 是

英文摘要：

Androgen receptor targeting remains the primary therapeutic strategy in prostate cancer, encompassing androgen biosynthesis inhibitors and androgen receptor antagonists. While both androgen-receptor-positive and “castration-resistant” prostate cancer are responsive to these approaches, the development of resistance is an almost inevitable outcome leading to the castration-resistant form of the disease. Given that “cytoprotective” autophagy is considered to be a predominant mechanism of resistance to various chemotherapeutic agents as well as to radiation in the cancer literature, the purpose of this review is to evaluate whether autophagy plays a central role in limiting the utility of androgen deprivation therapies in prostate cancer. Unlike most of our previous reports, where multiple functional forms of autophagy were identified, making it difficult if not impossible to propose autophagy inhibition as a therapeutic strategy, the cytoprotective form of autophagy appears to predominate in the case of androgen deprivation therapies. This opens a potential pathway for improving the outcomes for prostate cancer patients once effective and reliable pharmacological autophagy inhibitors have been developed.

摘要翻译： 

雄激素受体靶向治疗仍是前列腺癌的主要治疗策略，包括雄激素生物合成抑制剂和雄激素受体拮抗剂。尽管雄激素受体阳性和"去势抵抗性"前列腺癌均对这些治疗方法有反应，但耐药性的发展几乎是不可避免的结果，最终导致疾病进展为去势抵抗型。鉴于在癌症文献中，"细胞保护性"自噬被认为是多种化疗药物及放疗产生耐药性的主要机制，本综述旨在评估自噬是否在限制雄激素剥夺疗法治疗前列腺癌的疗效中发挥核心作用。与我们以往多数研究中发现自噬存在多种功能形式（这使得提出抑制自噬作为治疗策略变得困难甚至不可能）不同，在雄激素剥夺疗法中，细胞保护性自噬似乎占据主导地位。一旦开发出有效可靠的药物性自噬抑制剂，这为改善前列腺癌患者的治疗结局开辟了潜在途径。

原文链接：

Making the Case for Autophagy Inhibition as a Therapeutic Strategy in Combination with Androgen-Targeted Therapies in Prostate Cancer